Genetic manipulations and subsequent analysis of cells in culture have provided a wealth of information concerning the molecular and biochemical mechanisms that regulate diverse functions on a cellular level. However, in vitro models do not recapitulate the complex cell-cell interactions (juxtacrine, paracrine, or endocrine) that occur in vivo. Therefore, it is important to examine the effects of specific gene products in the context of the whole animal. This is particularly important for the study of diabetes- a polygenic disorder that involves numerous tissues and is also affected by environmental factors. By using wellcharacterized transcriptional regulatory elements and molecular techniques, it is now possible to generate animals that either express foreign genes or have endogenous genes inactivated/mutated within specific cells or tissues of the body (1,2). Although the concepts involved in generating such transgenic (Tg) or knockout/knockin (KO/KI) animals are fairly straight forward, the equipment, facilities, and personnel with the appropriate technical skills are either impractical or too expensive for most labs to implement. In response to enthusiastic demand for assistance in the generation of genetically altered mice, the proposed DRTC Transgenic Core is designed to provide the necessary expertise, facilities, equipment, and personnel to efficiently generate Tg and KO/KI mice for DRTC members. To accomplish this, the proposed Core will utilize a pre-existing, in house, highly successful core facility- the Washington University Mouse Genetics Core. This will preclude the need for the DRTC Transgenic Core to purchase and set up expensive equipment and independently hire/train/manage our own personnel. Thus, allocated funds can be used to immediately generate and analyze mice. It should be noted that analyses of animals generated through the proposed Core could also require expertise that does not exist in the laboratories of all users. The proposed DRTC Mouse Phenotyping Core will assist these users in the analysis of their animals. Thus, the complementary services of the DRTC Transgenic and Phenotyping Cores will enable users to focus on answering important biological questions rather than how to overcome technical hurdles.